Investigations of the association between benzodiazepine therapy and cognitive decline in elderly patients have yielded mixed findings. Stronger links have emerged from studies examining longer- rather than shorter-acting benzodiazepines, longer rather than shorter durations of use, or earlier rather than later exposure. Questions remain about causality and the impact of confounders on study interpretation.

Objective: To review the clinical pharmacology, efficacy, and safety of romosozumab, a humanized monoclonal antibody with a novel mechanism of action for monthly injection, and its place in the management of osteoporosis. Data Sources: PubMed, MEDLINE, and ClinicalTrials.gov searches (1966 to July 2020) were conducted using the keywords romosozumab and osteoporosis. Study Selection and Data Extraction: Published phase 2 and 3 clinical trials and 2 meta-analyses in patients with osteoporosis were included. Data Synthesis: Romosozumab increased bone mineral density (BMD) at the lumbar spine (12.1%-13.3%), femoral neck (2.2%-5.9%), and total hip (2.5%-6.9%) in patients with osteoporosis. After 12 months, romosozumab provided greater BMD gains at the lumbar spine and hip than teriparatide. However, teriparatide is likely to further increase BMD if continued for up to 24 months. In postmenopausal women at a high fracture risk, 1 year of romosozumab followed by 1 year of alendronate resulted in lower vertebral, nonvertebral, clinical, and hip fractures than alendronate alone for 2 years. Although absolute event rates were low, serious cardiovascular and cerebrovascular events were numerically higher in 2 clinical trials when compared with alendronate (2.5% vs 1.9%, respectively) and placebo (4.9% vs 2.5%, respectively). Relevance to Patient Care and Clinical Practice: This review discusses the place in therapy for romosozumab in osteoporosis management as a novel agent. Conclusions: Romosozumab offers an alternative for patients with a high risk of osteoporotic fractures. Clinicians should avoid romosozumab in patients with a history of myocardial infarction or stroke in the past 12 months.

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Aclidinium bromide is a novel, inhaled, long-acting anticholinergic that, when administered at the FDA-approved dose, safely produces clinically and statistically significant bronchodilation and improves health status in patients with moderate to severe COPD. Long-term clinical trials assessing the efficacy and safety of aclidinium are warranted.

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacokinetics, pharmacology, clinical efficacy, or safety of IDegLira in humans. Data Synthesis: IDegLira displayed pharmacokinetic and pharmacodynamic properties similar to that of the individual components. IDegLira has shown significant hemoglobin A1C (A1C) reductions of 1.3% to 1.9% and fasting plasma glucose reductions of 45 to 65 mg/dL when used in patients with T2DM previously receiving oral antihyperglycemic agents (AHAs), GLP-1 RAs, or basal insulin. Weight loss also occurred when IDegLira was started in patients previously receiving oral AHAs or basal insulin. Adverse effects (AEs) tended to be mild and transient. The most common AEs were headache, nasopharyngitis, upper-respiratory infections, and gastrointestinal disorders. Hypoglycemia risk was lower with IDegLira than basal insulin alone but higher than liraglutide alone. Conclusions: IDegLira may provide additional glycemic control with fewer AEs for patients uncontrolled on a GLP-RA or basal insulin alone. Additional studies evaluating use in patients on oral AHAs with higher A1C values and in comparison to bolus insulin are needed.

Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings. The current article examines published trials of valproic acid in the treatment of patients with dementia to identify whether an optimal dosing strategy exists. Secondarily, valproic acid dosing from published studies is compared with a real-world 5-year sample of valproic acid prescribing. Twenty studies met selection criteria and were included in the review. Based primarily on uncontrolled trials and the current retrospective study, valproic acid serum levels between 40 and 60 mcg/mL and relatively low doses (ie, 7-12 mg/kg per d) are associated with improvements in agitation in some patients with dementia. At the same time, similar valproic acid levels produced no significant behavioral improvements in most placebo-controlled studies and led to substantial side effects in some patients. Considerable trial design differences exist between controlled and uncontrolled trials. Overall, valproic acid appears to have limited efficacy as monotherapy in many patients with dementia. Its optimal role may be in combination with other psychotropics as a treatment of agitation associated with dementia.

Anticonvulsants are a class of medications that have received considerable interest as possible treatments in patients with behavioural disturbances in dementia. The role of these medications for such a use remains controversial. The current paper reviews the published evidence surrounding the safety and efficacy (i.e. as a behavioural and cognitive treatment) of newer anticonvulsants in patients with dementia. A MEDLINE, International Pharmaceutical Abstracts, PsycINFO and clinicaltrials.gov search through to December 2011 was conducted for anticonvulsants that have received regulatory approval since 1996. Studies reporting behavioural or cognitive outcomes in patients with dementia were included. Nine trials involving only four medications met selection criteria and were included: levetiracetam (n = 4), oxcarbazepine (n = 1), topiramate (n = 2) and zonisamide (n = 2). Levetiracetam may have a role in the treatment of behavioural symptoms in dementia but study limitations substantially hinder the strength of such a recommendation. Oxcarbazepine and topiramate, based on limited data, do not appear to be effective treatments of behavioural symptoms in dementia. A lack of trials do not allow for conclusions to be made regarding zonisamide. From a cognitive standpoint, levetiracetam was the anticonvulsant most examined in patients with dementia, it appears to have less deleterious effects than some anticonvulsants. Limited data are available on the safety of these medications in elderly patients; however, studies completed thus far have demonstrated some adverse events that are more common or problematic with the use of these drugs in this patient population (i.e. somnolence, dizziness, hyponatraemia, weight loss).

Osteoporosis is a leading cause of debility and declining quality of life in postmenopausal women worldwide. Treatment of osteoporosis has been ubiquitous throughout the developed world since the mid-1990s, most notably with the introduction of bisphosphonates in 1995. Nonetheless, the incidence of hip fractures increased by 25% between 1990 and 2000, despite advances in osteoporosis therapy. Studies indicate that bone density increases over the first 3 years of bisphosphonate therapy and then plateaus or perhaps even declines, placing these patients at greater risk of fracture. Since hip fractures are associated with increased morbidity, mortality, and increased cost of health care, improvements in treating osteoporosis are critical. Denosumab is a novel monoclonal antibody targeted against the receptor activator of nuclear factor-κB ligand (RANKL) that inhibits osteoclast activity. Initial data suggest that denosumab increases bone mineral density for greater than 3 years. Of greater importance, denosumab has been shown to decrease vertebral fractures by 68%, nonvertebral fractures by 19%, and hip fractures by 42% for at least 36 months. Data also indicate that the safety profile of denosumab is equivalent to other drugs used in osteoporosis management, but potential risks of immunosuppression and cancer have been hypothesized.